Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
EBioMedicine. 2019 Mar;41:286-298. doi: 10.1016/j.ebiom.2018.12.049. Epub 2019 Feb 21.
The low expression of miR93/25 (members of miR-106b25 cluster) promoted the invasion and metastasis of colon cancer cells, which predicted poor survival. However, the role of miR-106b-5p, the member of miR-106b25 cluster, in colorectal cancer (CRC) remains unclear.
Bioinformatics methods were used to predict the potential pairs of lncRNA-miRNA-mRNA. In situ hybridization and qPCR were used to evaluate the expression of MALAT1 and miR-106b-5p in the paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemistry staining was applied to investigate the expression of SLAIN2. Fluorescence recovery after photobleaching assay was applied to observe the microtubule (MT) mobility. In vitro and in vivo invasion and metastasis assays were used to explore the function of MALAT1/miR-106b-5p/SLAIN2 in the progression of CRC.
miR-106b-5p was identified as a suppressor in CRC. Functionally, ectopic or silencing the expression of miR-106b-5p inhibited or promoted the invasion and metastasis of CRC cells in vitro and in vivo. The long non-coding RNA MALAT1 regulated the miR-106b-5p expression and further mediated the mobility of SLAIN2-related MTs by functioning as a competing endogenous RNA in vitro and in vivo, which resulted in the progression of CRC. Clinically, low miR-106b-5p expression predicted poor survival of CRC patients, especially in combination with high MALAT1/ SLAIN2 expression.
miR-106b-5p served as a suppressor in combination with MALAT1/miR-106b-5p/SLAIN2, which might be a group of potential prognostic biomarkers in the prognosis of CRC. FUND: This work was supported by National Program Project for Precision Medicine in National Research and Development Plan of China (2016YFC0905300), National Natural Science Foundation of China (81572930), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0905303, 2016YFC1303200), Beijing Science and Technology Program (D17110002617004), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32012), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), Incentive Fund for Academic Leaders of Oncology Hospital, Chinese Academy of Medical Sciences (RC2016003), and Beijing Hope Run Special Fund from Cancer Foundation of China (LC2017A19). The project of Shanghai Jiaotong Univversity (YG2017QN30).
miR93/25（miR-106b25 簇的成员）的低表达促进了结肠癌细胞的侵袭和转移，这预示着预后不良。然而，miR-106b-5p（miR-106b25 簇的成员）在结直肠癌（CRC）中的作用尚不清楚。
使用生物信息学方法预测 lncRNA-miRNA-mRNA 的潜在对。使用原位杂交和 qPCR 评估石蜡包埋的正常和 CRC 组织中 MALAT1 和 miR-106b-5p 的表达。Kaplan-Meier 分析和对数秩检验用于生存分析。免疫组织化学染色用于研究 SLAIN2 的表达。荧光恢复后光漂白实验用于观察微管（MT）的流动性。体外和体内侵袭和转移实验用于研究 MALAT1/miR-106b-5p/SLAIN2 在 CRC 进展中的功能。
miR-106b-5p 被鉴定为 CRC 的抑制因子。功能上，外源性或沉默 miR-106b-5p 的表达抑制或促进了 CRC 细胞的体外和体内侵袭和转移。长非编码 RNA MALAT1 通过作为竞争内源性 RNA 在体外和体内调节 miR-106b-5p 的表达，并进一步介导 SLAIN2 相关 MT 的流动性，从而导致 CRC 的进展。临床上，低 miR-106b-5p 表达预示着 CRC 患者的预后不良，尤其是与高 MALAT1/SLAIN2 表达相结合时。
miR-106b-5p 与 MALAT1/miR-106b-5p/SLAIN2 结合作为抑制因子，可能成为 CRC 预后的一组潜在预后生物标志物。
本研究得到国家精准医学研究与发展计划重大项目（2016YFC0905300）、国家自然科学基金（81572930）、国家重点研发计划（2016YFC0905303、2016YFC1303200）、北京市科学技术计划（D17110002617004）、中国医学科学院中央级公益性科研院所基本科研业务费（2018PT32012）、中国医学科学院肿瘤医院创新基金（CIFMS）（2016-I2M-1-001）、中国医学科学院肿瘤医院学术带头人激励基金（RC2016003）、北京希望马拉松专项基金（LC2017A19）和上海交通大学项目（YG2017QN30）的支持。
